Evidence map›Paper›PMID 42646368›Full record

ArticleNeurology international2026

Brivaracetam in Combination with Midazolam and Ketamine Reduces Soman-Induced Seizure and Neurodegeneration in Rats.

Lucille A Lumley, Hailey G Steier, Sabrina Y Orta, Donna A Nguyen, Michael F Stone, Caroline R Schultz, Jerome Niquet, Marcio de Araujo Furtado, Claude G Wasterlain

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In one paragraph

Article in Neurology international, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Lucille A LumleyNeuroscience Department, U.S. Army Medical Research Institute of Chemical Defense (USAMRICD), Aberdeen Proving Ground, Aberdeen, MD 21010, USA.ORCID 0000-0003-4162-8817
Hailey G SteierNeuroscience Department, U.S. Army Medical Research Institute of Chemical Defense (USAMRICD), Aberdeen Proving Ground, Aberdeen, MD 21010, USA.
Sabrina Y OrtaNeuroscience Department, U.S. Army Medical Research Institute of Chemical Defense (USAMRICD), Aberdeen Proving Ground, Aberdeen, MD 21010, USA.
Donna A NguyenNeuroscience Department, U.S. Army Medical Research Institute of Chemical Defense (USAMRICD), Aberdeen Proving Ground, Aberdeen, MD 21010, USA.
Michael F StoneNeuroscience Department, U.S. Army Medical Research Institute of Chemical Defense (USAMRICD), Aberdeen Proving Ground, Aberdeen, MD 21010, USA.
Caroline R SchultzNeuroscience Department, U.S. Army Medical Research Institute of Chemical Defense (USAMRICD), Aberdeen Proving Ground, Aberdeen, MD 21010, USA.ORCID 0000-0002-3194-5993
Jerome NiquetDepartment of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Marcio de Araujo FurtadoBioSEaD, LLC, Rockville, MD 20850, USA.
Claude G WasterlainDepartment of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.

Funding

Rational polytherapy in the treatment of cholinergic seizuresU01NS074926 · NINDS · BRENTWOOD BIOMEDICAL RESEARCH INSTITUTE · PI WASTERLAIN, CLAUDE G · 2011 to 2015
$3.3M
National Institute of Allergy and Infectious Diseases AOD26011-001-00000NINDS NIH HHS U01 NS074926
6 · The paper itself

Abstract

BACKGROUND/

objectiveStatus epilepticus (SE) is a life-threatening condition that requires immediate response to effectively control. Although benzodiazepines are the first-line treatment against SE, when treatment is delayed, benzodiazepine pharmacoresistance develops. In preclinical models of benzodiazepine refractory SE, the addition of antiseizure medications (ASMs) as adjunct to midazolam to reduce neuronal excitability and enhance inhibitory function is essential to protect against the neurodegeneration and epileptogenesis that follows prolonged seizure. Brivaracetam is a recently FDA-approved ASM to treat partial onset seizures in pediatric and adult patients as a monotherapy or adjunct therapy. We evaluated the potential of brivaracetam as monotherapy or in combination with midazolam and ketamine for efficacy against organophosphorus nerve agent (OPNA)-induced refractory SE in rats.

methodsAdult male rats were exposed to a seizure-inducing dose of soman and treated with atropine sulfate and the oxime asoxime chloride one minute after soman exposure and with brivaracetam alone or in combination with midazolam and ketamine 40 min after seizure onset. Multiple metrics of protection such as seizure severity, spontaneous recurrent seizure (SRS), neuronal loss, and neuroinflammation were evaluated.

resultsAlthough brivaracetam monotherapy resulted in 100% survival, protection from the development of SRS and neurodegeneration only occurred when brivaracetam was administered as an adjunct to ketamine and midazolam. Initial seizure severity was also reduced by the combination of brivaracetam-midazolam-ketamine over monotherapy.

conclusionsAlthough further research is needed to determine optimal drug combinations, these preclinical findings provided further evidence that simultaneous polytherapy with ASMs improves OPNA-induced seizure outcomes.

Indexed as

antiseizure medicationcholinergicepileptogenesisorganophosphorus nerve agentpharmacoresistance

Identifiers

PMID42646368
PMCPMC13516675

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